Funding for this project, Nutritional Etiology of Pre-Diabetic Autoimmunity, began in May 1997 and allowed us to create and follow two unique cohorts of children. The first is a cohort of children who have a known risk for diabetes because they a) had been typed for diabetes-related HLA genotypes through a cord blood screening of over 30,000 general population children or b) are a sibling or offspring of someone with type 1 diabetes. This cohort is followed longitudinally for the development of diabetes-related autoimmunity. The second cohort consists of children who have tested positive for at least one diabetes autoantibody and who are followed over time to determine risk factors for conversion to diabetes. These two cohorts have been identified through the Diabetes Autoimmunity Study in the Young (DAISY) (R01-DK32493). A prospective follow-up of these cohorts has already provided important new information concerning the roles of cereal in the infant diet and in utero exposure to vitamin D on risk of islet autoimmunity, as well as predictors of oxidative stress in healthy children. In this competitive renewal application, we are proposing to extend the follow up of these cohorts in order to continue to address the original specific aims concerning anti-oxidants and oxidative stress, as well as investigate additional research areas that we have proposed based on our preliminary findings, including the roles of gut permeability and cereal grains, obesity and its associated inflammation, and gene-nutrient interactions. New findings from the Nutritional Etiology of Pre-diabetic Autoimmunity study will be valuable to the ongoing investigation of the nutritional causes of type 1 diabetes;and our study will continue to act as a pivotal vanguard project to the dietary studies of The Environmental Determinants of Diabetes in the Young study (TEDDY, U01-DK63821), particularly as our study children pass through the highest risk age group for type 1 diabetes.